Neglected Tropical Diseases (NTDs)

Question 1

Neglected Tropical Disease examples - Helminth NTD

Answer 1

Helminth: caused by parasitic worms
- Taeniasis/ Cysticerosis
- Guinea worm disease
- Enchinococcosis
- Foodborne termatodiasaes
- Soil-transmitted helminthiases
- Schistosomiasis
- Onchocerciasis

Question 2

Neglected Tropical Disease Examples - Protozoan NTDs

Answer 2

• Chagas Disease
• Leishmaniasis
• Human African Trypanosomiasis

Question 3

Fungal NTDs examples:

Answer 3

• Mycetoma
• chromoblastomycosis
• other deep mycoses

Question 4

Viral NTDs:

Answer 4

Rabies
Dengue&Chikungunya

Question 5

Bacterial NTDs

Answer 5

Buruli Ulcer
Leprosy
Trachoma
Yaws

Question 6

Non-infectious diseases or conditions (NTDs)

Answer 6

Snakebite envenoming

Question 7

Ectoparasitic NTDS

Answer 7

Scabies
Other Parasites

Question 8

What are NTDs

Answer 8

-Name changing to Neglected Infectious Diseases
- Undefined taxonomic group
- Mainly tropical diseases outside teh big three (HIV/TB/Malaria) with low visibility and fewer resources
-Low asymptomatic/incubation periods
- Disproprtionally affect bottom billion (refers to approximately one billion people living in extreme poverty)

Question 9

Prevalence

Answer 9

-Approx 1.7 billion in need of prevention or treatment
- 200,00 deather per year
- High level of diability

Question 10

Stigma and health imapct
The EDCTP

Answer 10

• Visual lifelong symptoms: mucosal/ limb infections
• Health seeking behaviour affected: Genital-related infections
• School attendance drops during infection/treatment of children
• Causes are often poverty related: washing in certain rivers, interaction with certain biting insects.

This stimga impacts life quality, mental health and treatment options

EDCTP:European & Developing Countries Clinical Trials Partnership, partnership of european and african countries to tackle diseases affecting sub-saharan africa.
Have a portfolio of drugs, vaccines and diagnostics for various diseases including NTDs

Question 11

NTDs:3 main Forms of Leishmaniasis

Answer 11

Cutaneous: Open sores at the site of bite
Mucocutaneous: Skin and mucus such as mouth and nose. Visceral: Infects liver, spleen, other organs: Can cause post-kala-azar dermal leishmaniasis (PDKL)- post treatment rash

Question 12

Leishmaniasis Epidemiology

Answer 12

Visceral: 50-90k/year, 20-30k deaths
Cutaneous: 600k-1M/year, no mortaility
Statistisc for mucocutaneous lacking/ incomplete.

Question 13

Leishmaniasis diagnosis - sample acquisition

Answer 13

Sample acquisition: Biopsy, punch or scaping of lesion fragments for Cutaneous Leishmaniasis: biopsy/ aspiration from bone marrow, lymph nodes or spleen for Visceral Leishmaniasis, serum for antibody detection of both clinical forms.

Question 14

Leishmaniasis diagnosis - Lab Diangosis techniques of Leishmaniasis

Answer 14

Microscopy: Visualisation of mamasigtoes with Giemsa/ haemotoxylin and oesin stains upon microsopic examination of tissue specimens. In vitro and in vivo isolation: Promastigotes can be a biphasic medium using a blood agar base. Inoculation of mice/hamsters can isolate parasites. In vivo immune response: cutaneous: skin test measures delayed-type hypersensitivity to parasite anitgens. Antibody detection: Mainly used for Visceral. Commonly used techniques: ELISA, RDT, ICT (using recombinant antigens like rK39) for VL. ELISA and Western Blot used for CL. Molecular diagnosis: Based mainly on amplification via PCR. Common detection and typing techniques: PCR, DNA sequencing and LAMP

Question 15

Leishmaniasis Treatment (mostly VL)

Answer 15

Visceral: most severe/ fatal - bigger health concern so more drugs available.
Sodium stibogluconate (SSG) , Amphotericin B - cutaenous too, Liposomal amphotericin B, Miltrefosine - cutaenous, Patamyomocyin, Pentamidine- cutaneous.
Cutaneous, mucocutaneous: topical treatments, heat therapies ( targeting parasites in skin lesions), systemic medications in more severe cases ( antimonial medications), surgery, combination therapies.

Question 16

Protozoa

Answer 16

• Aka protists
• Singular terms: protozoan or protist

Eukaryotic microorganisms. Originally thought to be animals due to lack of cell wall and their motility. Vast variety of cell functions, locomotion, genetic structure and life cycles. Mostly independent in various terrestrial and aquatic environments: soil, freshwater, and marine habitats). Usually require high moisture environment for propagation.

Question 17

Protozoan reproduction methods

Answer 17

Asexually: binary or multiple fission or sexually.

Question 17

Protozoan lifecycle

Answer 17

-Most have trophozoite (active feeding stage)
- Usually the stage inside the host for parasites
- May be various sub-stages inside this E.g. presence/absence of flagellum
- Some form a cyst: dormant and infectious, survive pH and temperature changes. Parasites: many forms are in different hosts/ vectors

Question 18

Leishmania spp.

Answer 18

Hemoflagellated protists that transmit via sand flies: Blood parasite with a flagellum. Infect a wide variety of vertebrates. 2 cell types during life cycle: Promastigote (a), Amastigote (b). Lipophosphoglycan (LPG) on cell surface: Interacts with host, Major virulence factor.

Question 19

Leishmania old and new world psecies

Answer 19

Multiple species cause leishmaniasis e.g
Old world species (blue): L. tropica- cutaneuos, L.major, L. donovani-visceral
New world species (red): L. mexicana
L braziliensis complex - group associated with cutaneous and mucocutaneous
L. infantum (sometimes)

Question 20

Features of Leishmania genomics

Answer 20

32Mbp in size (small): undergo gene loss/chromosomal rearrangements during adaptation. 36 chromosomes: New World Leishmania have 34 or 35. ~8300 protein encoding genes. ~910 RNA genes: high density to maximise gene expression/ metabolic efficiency. Mitochondrion and kinetoplast also present. No transcription factors: Gene expressions not tightly controlled: Post-translation modification occurs. Genome is aneuploid: Different copies of each chromosome. Can change copy number during life cycle and in response to stress.

Question 21

Leprosy

Answer 21

aka Hansens Disease. two main types: PB and MB.

Question 22

Leprosy PB characteristics

Answer 22

Skin lesions; 1-5 including single nerve lesion if present. Peripheral nerve involvement: No nerve/ only one with or without 1-5 lesions. Skin smears: Negative at all sites

Question 23

Leprosy MB characteristics

Answer 23

Skin lesions: 6 and above. Peripheral nerve involvement: More than one nerve irrespective of number of skin lesions. Skin smears: Positive at any site

Question 24

Leprosy clinical classifications

Answer 24

TT: polar tuberculoid BT: borderline tuberculoid, BB: borderline-borderline, BL: borderline lepromatous , LL: polar lepromatous

Question 25

Leprosy signs and symtpoms

Answer 25

Numbness or tingling in hands or feet. Weakness of hands feet or eyelids. Loss or decrease of sensation in the skin patches. Painful nerves. Swelling or lumps in face or earlobes. Painless wounds or burns on hands or feet. Dark-skinned people may have light patches on the skin, white pale-skinned people have darker or reddish patches.

Question 26

Leprosy - epidemiology

Answer 26

• 200K per year
• Stable: long incubation/ chronic nature of infection mean cases go undetected for a long time: cases accumulate gradually. Low infectivity and effective control measures reduces transmission ( usually due to prolonged close contact with infected)/ outbreaks

Question 27

Leprosy diagnosis (confirmation)
treatments

Answer 27

Molecular or phenotypic. Immunological markers also used: Anti-PGL 1

Blister packs fro treatment

Question 28

Mycobacterium Leprae

Answer 28

First ever bacterium confirmed to cause disease. Close relative of M. tuberculosis and M. ulcerans: M. ulcerans causes another NTD, Buruli ulcer. Very slow replication rate: 14 day doubling time. Obligate intracellular parasite: Cannot be cultured so its Grown in mouse, rabbits or armadillos (or squirrels) for tissue/ specific host gene/ immune pathway susceptibility analysis.

Spread via respiratory droplets (M.lepare shed nasally): Rapid diagnostic works on nasal swabs via PCR, LAMP . Also use specimen genome sequencing.

Question 29

mycobacterium leprae genomics

Answer 29

3.3 Mb genome (bactierum relies heavily on host-derived nutrients: lost genes for biosynthetic/metabolic pathways unneeded in host environment). Massive reduction of functionality; Large number of pseudogenes. Difficulty in culturing/WGS means little known about diversity